Genotype replacement of the human parainfluenza virus type 2 in Croatia between 2011 and 2017 – the role of neutralising antibodies

Abstract

Previously we reported on the HPIV2 genotype distribution in Croatia 2011-2014. Here we expand this period up to 2017 and confirm that G1a genotype has replaced G3 genotype from the period 2011-2014. Our hypothesis was that the G1a-to-G3 genotype replacement is an antibody-driven event. A cross-neutralisation with anti-HPIV2 sera specific for either G1a or G3 genotype revealed the presence of genotype-specific antigenic determinants. By the profound, in silico analyses three potential B cell epitopic regions were identified in the hemagglutinin neuraminidase (regions 314-361 and 474-490) and fusion protein (region 440-484). The region identified in the fusion protein does not show any unique site between the G1a and G3 isolates, five differentially glycosylated sites in the G1a and G3 genotype isolates were identified in epitopic regions of hemagglutinin neuraminidase. All positively selected codons were found to be located either in the region 314-316 or in the region 474-490 what indicates a strong positive selection in this region and reveals that these regions are susceptible to evolutionary pressure possibly caused by antibodies what gives a strong verification to our hypothesis that neutralising antibodies are a key determinant in the inherently complex adaptive evolution of HPIV2 in the region.

Virological Surveillance and Molecular Characterization of Human Parainfluenzavirus Infection in Children with Acute Respiratory Illness: Germany, 2015–2019

“…Ours is the first study to provide HN gene sequences including phylogenetic characterization for HPIV types 1–4 from Germany, and, to our knowledge, it is one of only five studies providing HN gene sequence data from HPIV circulating in Europe [ 10 , 11 , 74 , 75 ].…”

“…Clusters G1 and G2 constituted the first cluster identified by Terrier et al, while Clusters G3 and G4 constituted the second cluster identified by Terrier et al, respectively. The molecular characterization of additional HPIV-2 isolates collected between 2011 and 2017 led to the determination of more HPIV-2 sequences, which were categorized into the predefined clusters G1 and G3 [ 10 , 39 ]. Cross-neutralization activity between Clusters G1 and G3 was low, indicating the existence of distinct genotype-specific antigenic determinants [ 10 ].…”

“…Of these, the hemagglutinin-neuraminidase (HN) and the fusion (F) protein are surface glycoproteins that are major antigenic determinants [ 1 , 5 , 6 ]. The HN gene, which displays a high degree of genetic variability, has been the basis of most HPIV molecular epidemiology studies to date [ 7 , 8 , 9 , 10 , 11 ].…”

“…However, the HPIVs circulating worldwide rarely undergo molecular characterization. Phylogenetic analyses are published sporadically only, often in the context of single-location studies and involving only one of the four known HPIV types [ 10 , 11 , 21 , 35 , 36 , 37 , 38 , 39 , 40 , 41 ]. As a result, HPIV sequence information available in the public domain is scarce; at the time of this writing, a total of 2633 hemagglutinin-neuraminidase (HN) gene or whole-genome sequences were available at GenBank (HPIV1: 530, HPIV2: 169, HPIV3: 1793, HPIV4: 141; GenBank query version 04/30/2021).…”

Genetic Characteristics of Human Parainfluenza Virus Types 1–4 From Patients With Clinical Respiratory Tract Infection in China

“…Phylogenetic analyses showed that different genetic lineages of HPIV3 in sub-cluster C3 co-circulated in China, with C3f as the dominant lineage according to the HN gene sequence. Based on the phylogenetic tree of the HN gene of HPIV2 in a previous study (Santak et al, 2018), G1c was defined as a new sub-cluster in this study. Two HPIV4 sequences belonged to cluster 4A, and cluster 4B was not found in this study.…”